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Regular intake of caffeinated but not decaffeinated coffee attenuates behavioral modifications in mice subject to chronic unpredictable stress.

Created on 24 Jul 2026

Authors

Ângelo R Tomé, Nuno J Machado, Ana Paula Ardais, Ana Nunes, Henrique B Silva, Manuella P Kaster, Paula Agostinho, Rodrigo A Cunha

Published in

Neurobiology of stress. Volume 44. Pages 100838. Epub Jul 16, 2026.

Abstract

The regular intake of moderate doses of coffee is increasingly recognized as a lifestyle factor associated with a lower incidence of depressive-like conditions; however, there is still a debate on the relative effects of caffeinated and decaffeinated coffee. We now resorted to a model of chronic unpredictable stress to compare how the regular drinking of caffeinated and decaffeinated coffee impacted on stress-induced deterioration of mood and memory in adult mice. Stressed mice displayed lower weight gain, increased locomotion and greater anxiety, lower motivation in the splash test, less struggling and greater immobility in the forced swimming test, increased anhedonia in the sucrose preference test and decreased spatial reference memory in the object displacement and modified Y-maze tests. The continuous intake of caffeinated, but not decaffeinated, coffee attenuated all these stress-induced mood and memory deficits. Moreover, the intake of caffeinated, but not decaffeinated coffee, also attenuated the stress-induced decrease of long-term potentiation in hippocampal synapses and of brain-derived neurotrophic factor levels in frontocortical synapses, a neurophysiological and neurochemical signature of mood deterioration. These results prompt caffeine as a prominent coffee constituent responsible for the benefits of the regular intake of coffee on stress-induced behavioral deficits.

PMID:
42495655
Bibliographic data and abstract were imported from PubMed on 24 Jul 2026.

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